Hashimotos

"Hashimoto's thyroiditis or chronic lymphocytic thyroiditis is an
autoimmune disease in which the thyroid gland is gradually destroyed by a
variety of cell and antibody mediated immune processes." Wikipedia

Actually, there are two forms of Hashimoto's that are of concern in DS.

Hashimoto's thyroiditis

Hashimoto's encephalopathy

Hashimoto's Thyroiditis

"Abnormal physiologic functioning affects thyroid metabolism and
intestinal malabsorption. Frequent infections are presumably due to
impaired immune responses, and the incidence of autoimmunity, including hypothyroidism and rare Hashimoto thyroiditis, is increased...

"Endocrine system

Hashimoto thyroiditis that causes hypothyroidism
is by far the most common acquired thyroid disorder in patients with
Down syndrome.6The onset is usually from school age onwards, but onset in infancy is reported.7

More rarely, Hashimoto thyroiditis can cause hyperthyroidism8; the incidence of Graves disease is also increased.9

The
prevalence rate of thyroid disorders, such as congenital
hypothyroidism, primary hypothyroidism, autoimmune thyroiditis, and
compensated hypothyroidism or hyperthyrotropinemia, is reportedly 3-54%
in individuals with Down syndrome and increases with increasing age.

"Hashimoto's Thyroiditis is the autoimmune thyroid disease that is the most common cause of
hypothyroidism, an underactive thyroid. A very rare condition associated with Hashimoto's Thyroiditis
is Hashimoto's Encephalopathy, a neuroendocrine disorder. Much like the antibodies in Hashimoto's
Thyroiditis attack the thyroid, in Hashimoto's Encephalopathy, antibodies attack neurons in the brain.
While Hashimoto's Encephalopathy is quite rare (there may only be several dozen diagnosed patients in
the U.S.) it is also likely that there are many more undiagnosed sufferers. Because it is little known and
its symptoms are primarily neurological, it is easy to misdiagnosis or overlook and the symptoms
frequently lead to mistaken neurological diagnoses.

"Some of the most common symptoms of Hashimoto's Encephalopathy include: disorientation, psychosis,
tremors, concentration and memory problems, jerks in the muscles and lack of coordination, headaches,
partial paralysis on the right side, and speech problems. Sometimes, patients are mistakenly diagnosed
as having had a stroke, or having Alzeimer's. Typically, Hashimoto's antibodies levels will be high, and
the patient may also have a diagnosable case of Hashimoto's Thyroiditis, but TSH levels may also be
normal.

"The condition can also appear in adolescents, but is even more likely to be overlooked. The symptoms
in adolescents, unlike adults, frequently include seizures, confusion and hallucinations. A drop in school
performance is also a common symptom, along with progressive cognitive decline. Thyroid autoantibody
levels should be evaluated in these adolescents with these symptoms, even when thyroid function tests
are normal.http://thyroid.about.com/cs/hashimotos/a/encephalopathy.htm

The prevalence of autoimmune
disease is much higher in Down Syndrome (DS) than in the general
population. We have encountered 10 patients in the Duke DS Comprehensive
Clinic who developed cognitive regression, autistic characteristics,
and insomnia beginning in their early teenage years. These patients all
had thyroid autoimmunity without clinical thyroid disease. Cognitive and
developmental regression associated with thyroid autoimmunity has not
previously been described in children with DS. We are naming this
condition DS Disintegrative Disorder (DSDD), because of its similarity
to Disintegrative Disorder in three to five year old typical children.
Hashimoto’s Encephalopathy (HE) is an autoimmune CNS disease associated
with but not caused by thyroid autoimmunity, most commonly reported in
adults, but also reported to occur in some children. Cerebral folate
deficiency is caused by either autoimmunity to a tissue folate receptor
or by abnormalities of folic acid metabolism. In children, cerebral
folate deficiency can also lead to autism, regression, and insomnia.
Chromosome 21 contains many genes for folate metabolism, folate
transport, and for enzymes that require folate for activity (including
N6ANTI).

The purpose of the study is to
characterize the clinical and laboratory findings in DSDD; evaluate
thoroughly all patients with DSDD for known metabolic causes of
regression; to test the hypotheses that antibodies to the tissue folate
receptor and to alpha enolase are present in some subjects; and to
evaluate subjects for evidence of abnormal folate metabolism.

Lay Summary of Proposed Project:

The prevalence of autoimmune
disease is much higher in Down syndrome (DS) than in the general
population. It appears that a subset of adolescent patients in the Duke
Comprehensive DS Clinic have experienced significant regression. We
would like to systematically evaluate these patients by review of
medical records, laboratory evaluations, neuropsychological evaluations,
and speech and language testing, and then compare the patients’ data to
draw conclusions about their similarities. We are going to test these
patients to see if they have a problem using folate correctly, and if
they do, our next step in a future study is to treat the patients with
folinic acid to see if their symptoms, such as learning, social
withdrawal, perseverative thoughts, or trouble sleeping improve with
treatment. Describing this subset of patients in the medical literature
will help other clinicians caring for people with DS identify this dual
diagnosis and monitor or treat these patients appropriately.